Sleep and circadian rhythms in bipolar disorder

The reduced need for sleep during manic episodes of bipolar disorder is well known, with periods of reduced sleep recognised as a prodromal feature of mania. But a closer look at sleep disturbances in people with bipolar disorder uncovers persistent problems with sleep and circadian rhythms even during periods of euthymia.

The two major structures in the brain that control circadian rhythms are the hypothalamus and the pineal gland, which secretes the sleep hormone melatonin. Dr Bruno Etain, an Associate Professor at the Université de Paris Est in France, described new findings on clinical and genetic factors related to abnormalities in circadian rhythms that have been associated with bipolar disorder.

From the clinical perspective, there is consistent evidence from actigraphy studies that increases in the sleep fragmentation index, sleep duration and sleep latency can distinguish bipolar disorder patients from healthy controls even during periods of remission. In fact, the intra-individual variability in sleep fragmentation could be a hallmark of bipolar illness that is useful both for diagnostic purposes but also potentially for predicting mood relapse. The potential contributions of actigraphy to personalized medicine are the subject of a study by Dr Etain’s group that is still in the planning stages.

Genetic mediators of circadian disturbances

Several genes involved in the regulation of melatonin production have been associated with circadian disturbances in bipolar disorder. Dr Etain described at least three gene variants that may predict susceptibility to bipolar disorder. His French colleagues have shown that specific genotypes are significantly associated with phenotypes in bipolar disorder, notably a more languid disposition (i.e., marked by fatigue and lack of energy) with variants in the TIMELESS gene, and more rigidity to changes in sleep patterns (i.e., marked by sensitivity to variations in circadian rhythms) with variants in the RORA gene. Carriers of other gene variants have been shown to relapse faster than non-carriers, and Dr Etain hypothesized that this could be driving some of the seasonal variations in relapses that are commonly observed in bipolar disorder.

Shining a new light on the management strategies

Whereas management strategies for sleep disturbances have been studied in the general population, there is a relative lack of evidence guiding optimal strategies to treat sleep problems in bipolar disorder patients. This is surprising given the high prevalence of sleep disorders in the bipolar population and their demonstrated deleterious consequences on patients’ quality of life, functioning and the risk of mood relapse.

Prof Gunnar Morken from the Norwegian University of Science and Technology in Trondheim, Norway, described management approaches to sleep disturbances that could be applied to bipolar disorder patients. Notably, for patients with delayed sleep onset phase problems, he recommends first stabilizing the circadian rhythm by establishing a set sleep schedule then gradually shifting the rise times towards the desired wake time by about 30 minutes every other week. He also encourages patients not to stay in bed when they are not sleeping as a strategy to avoid excessive time spent ruminating.

Dr Morken shared his belief that light strategies are under-utilized in the management of sleep disturbances in bipolar disorder. He advocated for the use of simple light strategies to normalize circadian rhythms in bipolar disorder patients. For example, intense light exposure after waking can help establish more appropriate wake times, and light blocking strategies in the evening can promote sleep onset and maintenance. One intriguing strategy is for patients to wear special glasses in the evening that block out blue light. This is because blue light impairs the body’s natural production of melatonin.

Screening out blue light

This raised an interesting discussion on the influence of rising rates of screen time in today’s culture and the potential impact on the course of bipolar disorder. Evidence has proven that computer, phone and tablet screens generate sufficient blue light to impair melatonin production, and newer generations of screens are delivering brighter light and higher levels of blue light. This could potentially spell bad news for people with bipolar disorders. Eyewear and Apps are available that can filter out blue light from standard screens to mitigate problems associated with sleep disturbances and eye strain.

Melatonin

Melatonin tablets are commonly recommended to bipolar disorder patients who have trouble sleeping, however there are few studies to guide the optimal dose and timing of administration. Anecdotally, some bipolar disorder patients are “melatonin responders” but others discern no noticeable effects. Dr Morken’s opinion was that melatonin tablets do not appear to be as effective as light blocking strategies for patients with problems with delayed onset sleep, since they may get a sufficient quantity of sleep but struggle with sleeping at the desired times.

The Future is bright

It was clear to this correspondent that the literature in this field is still in its infancy, and much more research is needed before the problems associated with disturbed sleep and circadian rhythms in bipolar disorder can be put to bed. Nonetheless, some exciting advances are sure to stimulate further work in the field.

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